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Peripheral Effects (peripheral + effects)
Selected AbstractsElectrical activation of the orbicularis oculi muscle does not increase the effectiveness of botulinum toxin type A in patients with blepharospasmEUROPEAN JOURNAL OF NEUROLOGY, Issue 3 2010A. Conte Background:, Our primary aim in this study was to determine whether electrically induced activation of the injected muscle increases effectiveness of botulinum type A toxin (BonT-A) in patients with blepharospasm (BPS). The second aim was to assess the safety of BonT-A by investigating whether BonT-A injection alters the excitability of blink reflex circuits in the brainstem. Methods:, Twenty-three patients with BPS received BonT-A (Botox) injected bilaterally into the orbicularis oculi muscle at a standard dose. In 18 patients, electrically induced muscle activation of the orbicularis oculi muscle on one side was performed for 60 min (4 Hz frequency) in a single session, immediately after BonT-A injection and in five patients for 60 min once a day for five consecutive days. The severity of BPS was assessed clinically with the BPS score. Compound muscle action potential (cMAPs) from the orbicularis oculi muscles were measured bilaterally. The blink reflex recovery cycle was studied at interstimulus intervals of 250 and 500 ms. Participants underwent clinical and neurophysiological assessment before BonT-A injection (T0) and 2 weeks thereafter (T1). Results:, Compound muscle action potential amplitude significantly decreased at T1 but did not differ between stimulated and non-stimulated orbicularis oculi in the two groups. BonT-A injection left the blink reflex recovery cycle tested on the stimulated and non-stimulated sides unchanged. Conclusions:, In patients with BPS, the electrically induced muscle activation neither increases the effectiveness of BonT-A nor produces larger electrophysiological peripheral effects. The lack of BonT-A-induced changes in the blink reflex recovery cycle provides evidence that BonT-A therapy is safe in patients with BPS. [source] The synthetic cannabinoid WIN55212-2 decreases the intraocular pressure in human glaucoma resistant to conventional therapiesEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 2 2001Anna Porcella Abstract The search for new ocular hypotensive agents represents a frontier of current eye research because blindness due to optic neuropathy occurs insidiously in 10% of all patients affected by glaucoma. Cannabinoids have been proposed to lower intraocular pressure by either central or peripheral effects but a specific mechanism for this action has never been elucidated. We recently demonstrated the presence of the central cannabinoid receptor (CB1) mRNA and protein in the human ciliary body. In the present study we show that the synthetic CB1 receptor agonist, WIN 55212,2, applied topically at doses of 25 or 50 µg (n = 8), decreases the intraocular pressure of human glaucoma resistant to conventional therapies within the first 30 min (15 ± 0.5% and 23 ± 0.9%, respectively). A maximal reduction of 20 ± 0.7% and 31 ± 0.6%, respectively, is reached in the first 60 min. These data confirm that CB1 receptors have direct involvement in the regulation of human intraocular pressure, and suggest that, among various classes of promising antiglaucoma agents, synthetic CB1 receptor agonists should deserve further research and clinical development. [source] Corticotropin-releasing factor decreases IL-18 in the monocyte-derived dendritic cellEXPERIMENTAL DERMATOLOGY, Issue 3 2009Hee Jung Lee Abstract:, Recent evidence suggests that crosstalk between mast cells, nerves and keratinocytes might be involved in the exacerbation of inflammatory conditions by stress, but the mechanism by which this occurs remains unclear. Corticotropin-releasing factor (CRF), which activates the hypothalamo-pituitary-adrenal (HPA) axis under stress, also has pro-inflammatory peripheral effects. However, there have been no reports about CRF receptor expression and the functional role of CRF in the dendritic cell (DC), which is considered to be the link between allergen uptake and the clinical manifestations of allergic diseases, such as atopic dermatitis. The purpose of this study was to investigate the expression of CRF receptors and the functional role of CRF in the monocyte-derived DC (MoDC) of atopic dermatitis patients and non-atopic healthy controls. In this study, mRNAs for CRF-R1, and 1,, as well as the CRF-R1 protein, were detected in MoDCs. CRF-R2, (but not R2, or R2,) mRNA and the CRF-R2 protein were present in MoDCs. Exposure of DCs to CRF resulted in a decrease of IL-18 in both atopic dermatitis patients and non-atopic healthy controls. However, CRF did not alter the expression of IL-6, CCL17, CCL18, and CCL22. Therefore, our results demonstrate that CRF could modulate immune responses by acting directly upon DCs. [source] Surgical treatment of migraine headaches.HEADACHE, Issue 3 2003B Guyuron Plast Reconstr Surg. 2002 Jun;109(7):2183-2189 This prospective study was conducted to investigate the role of removal of corrugator supercilii muscles, transection of the zygomaticotemporal branch of the trigeminal nerve, and temple soft-tissue repositioning in the treatment of migraine headaches. Using the criteria set forth by the International Headache Society, the research team's neurologist evaluated patients with moderate to severe migraine headaches, to confirm the diagnosis. Subsequently, the patients completed a comprehensive migraine headaches questionnaire and the team's plastic surgeon injected 25 units of botulinum toxin type A (Botox) into each corrugator supercilii muscle. The patients were asked to maintain an accurate diary of their migraine headaches and to complete a monthly questionnaire documenting pertinent information related to their headaches. Patients in whom the injection of Botox resulted in complete elimination of the migraine headaches then underwent resection of the corrugator supercilii muscles. Those who experienced only significant improvement underwent transection of the zygomaticotemporal branch of the trigeminal nerve with repositioning of the temple soft tissues, in addition to removal of the corrugator supercilii muscles. Once again, patients kept a detailed postoperative record of their headaches. Of the 29 patients included in the study, 24 were women and five were men, with an average age of 44.9 years (range, 24 to 63 years). Twenty-four of 29 patients (82.8 percent, p < 0.001) reported a positive response to the injection of Botox, 16 (55.2 percent, p < 0.001) observed complete elimination, eight (27.6 percent, p < 0.04) experienced significant improvement (at least 50 percent reduction in intensity or severity), and five (17.2 percent, not significant) did not notice a change in their migraine headaches. Twenty-two of the 24 patients who had a favorable response to the injection of Botox underwent surgery, and 21 (95.5 percent, p < 0.001) observed a postoperative improvement. Ten patients (45.5 percent, p < 0.01) reported elimination of migraine headaches and 11 patients (50.0 percent, p < 0.004) noted a considerable improvement. For the entire surgical group, the average intensity of the migraine headaches reduced from 8.9 to 4.1 on an analogue scale of 1 to 10, and the frequency of migraine headaches changed from an average of 5.2 per month to an average of 0.8 per month. For the group who only experienced an improvement, the intensity fell from 9.0 to 7.5 and the frequency was reduced from 5.6 to 1.0 per month. Only one patient (4.5 percent, not significant) did not notice any change. The follow-up ranged from 222 to 494 days, the average being 347 days. In conclusion, this study confirms the value of surgical treatment of migraine headaches, inasmuch as 21 of 22 patients benefited significantly from the surgery. It is also evident that injection of Botox is an extremely reliable predictor of surgical outcome. Comment: Many small placebo-controlled studies and much anecdotal literature suggests that botulinum toxin may be effective in prevention of migraine, perhaps to the same extent as conventional prophylactic treatment. Larger, randomized clinical trials are underway to resolve this issue. In the meantime, those who believe in the effectiveness of botulinum toxin prophylaxis argue about how it works, that is whether its antinociceptive properties are due to peripheral effects, central or presynaptic effects, or both. Dr. Guyuron's group favors the idea that botulinum toxin interrupts a reflex arc between the central nervous system (CNS) and peripheral musculature, and that after establishing efficacy by low dose botulinum injection in the corrugator supercilii muscles, surgical resection of these muscles results in prolonged and effective prophylaxis. The idea is radical but intriguing and should not be dismissed out of hand. However, a trial is necessary in which both the botulinum toxin injections are blinded with vehicle, and the study of the surgery involves a sham surgery control group with extended long-term follow-up, before these forms of prophylaxis can be recommended to patients. SJT [source] Pharmacology of the Selective 5-HT1B/1D Agonist FrovatriptanHEADACHE, Issue 2002M.B. Comer BSc Objective.,To determine the pharmacological profile of frovatriptan. Background.,Frovatriptan is a new 5-HT1B/1D agonist developed for the treatment of migraine. Methods.,Pharmacological studies were performed using in vitro and in vivo techniques. Results.,Radioligand-binding studies showed that frovatriptan has a high affinity for 5-HT1B and 5-HT1D receptors, and moderate affinity for 5-HT1A, 5-HT1F, and 5-HT7 receptors. In vitro, frovatriptan acts as a potent full agonist at human cloned 5-HT1B and 5-HT1D receptors, and as a moderately potent full agonist at 5-HT7 receptors. Studies of frovatriptan in isolated human arteries demonstrated a lower threshold for constriction of cerebral than coronary vasculature and a bell-shaped dose-response curve was apparent in the coronary arteries. In anesthetized dogs, frovatriptan administration produced no measurable effect on cardiac function or on blood pressure. Frovatriptan had no effects on coronary blood flow following transient coronary artery occlusion, whereas sumatriptan produced a prolonged and significant decrease in coronary blood flow. Conclusion.,The pharmacology of frovatriptan suggests that it should be an effective agent for the acute treatment of migraine, with a low potential for undesirable peripheral effects. [source] CB1 Receptor Blockade and its Impact on Cardiometabolic Risk Factors: Overview of the RIO Programme with RimonabantJOURNAL OF NEUROENDOCRINOLOGY, Issue 2008A. J. Scheen Rimonabant, the first selective CB1 receptor antagonist in clinical use, has been extensively investigated in the Rimonabant in Obesity (RIO) programme, comprising four 1,2 year placebo-controlled randomised clinical trials recruiting more than 6600 overweight/obese patients with or without co-morbidities. Rimonabant 20 mg daily consistently reduced body weight, waist circumference, triglycerides, blood pressure, insulin resistance and C-reactive protein levels, and increased HDL cholesterol concentrations in both non-diabetic and type-2 diabetic overweight/obese patients. Adiponectin levels were increased, an effect that correlated with HDL cholesterol augmentation, while small dense LDL cholesterol levels were decreased in patients receiving rimonabant 20 mg compared with those receiving placebo in RIO Lipids. Furthermore, in RIO Diabetes, a 0.7% reduction in glycated haemoglobin (HbA1c) levels was observed in metformin- or sulphonylurea-treated patients with type-2 diabetes, an effect recently confirmed in the 6-month SERENADE (Study Evaluating Rimonabant Efficacy in drug-NAïve DiabEtic patients) trial in drug-naïve diabetic patients. Almost half of metabolic changes occurred beyond weight loss, in agreement with direct peripheral effects. The positive effects observed after 1 year were maintained after 2 years. Rimonabant was generally well-tolerated, but with a slightly higher incidence of depressed mood disorders, anxiety, nausea and dizziness compared with placebo. In clinical practice, rimonabant has to be prescribed to the right patient, i.e. overweight/obese subjects with cardiometabolic risk factors and with no major depressive illness and/or ongoing antidepressive treatment, in order to both maximise efficacy and minimise safety issues. New trials are supposed to confirm the potential role of rimonabant in patients with abdominal adiposity, atherogenic dyslipidaemia and/or type-2 diabetes, i.e. at high cardiometabolic risk. [source] Quantitative Sensory Testing in Patients With Chronic Unilateral Radicular Neuropathic Pain and Active Spinal Cord StimulationNEUROMODULATION, Issue 3 2006Dirk Rasche MD Abstract Objectives., Spinal cord stimulation (SCS) is an effective treatment option for chronic radicular neuropathic pain syndromes. This prospective study was performed to examine the peripheral effects of SCS on sensation using quantitative sensory testing (QST). Materials and Methods., We measured two consecutive QST measurements for thermal, tactile-static, tactile-dynamic, vibratory, and pain sensation of the lower limbs in seven patients with chronic unilateral radicular neuropathic pain who underwent SCS implantation for their pain. Measurements were performed when SCS was turned off and once again during SCS and subsequent reduced pain levels. Results., Baseline QST demonstrated significantly increased thresholds for tactile and warm and cold detection in the pain area. With SCS active, a significant reduction of the cold and warm perception and mechanical detection thresholds was found on the painful side (p < 0.01). Although not significant (p > 0.01), altered sensory thresholds with active SCS also were found at the healthy side where no paresthesias were felt. Conclusion., SCS leads to bilateral subclinical effects even if the evoked paresthesias are only unilateral. Pain perception thresholds are not altered with therapeutic SCS. [source] Abnormalities of the HPA axis in affective disorders: clinical subtypes and potential treatmentsACTA NEUROPSYCHIATRICA, Issue 5 2006Richard J. Porter Background:, New evidence is emerging regarding abnormalities of hypothalamic-pituitary-adrenal (HPA) axis function in subtypes of affective disorders. Adverse effects of HPA axis dysregulation may include dysfunction of monoaminergic transmitter systems, cognitive impairment and peripheral effects. Newer treatments specifically targeting the HPA axis are being developed. Objective:, To review these developments focusing particularly on the glucocorticoid receptor (GR) antagonist mifepristone. Method:, A selective review of the literature. Results:, The function of GRs is increasingly being defined. The role of corticotrophin-releasing hormone (CRH) and dehydroepiandrosterone (DHEA) in the brain is also increasingly understood. HPA axis function is particularly likely to be abnormal in psychotic depression and bipolar disorder, and it is in these conditions that trials of the GR antagonist mifepristone are being focused. CRH antagonists and DHEA are also being investigated as potential treatments. Conclusion:, Initial studies of mifepristone and other HPA-axis-targeting agents in psychotic depression and bipolar disorder are encouraging and confirmatory studies are awaited. [source] | ||||||||||